In addition to reducing seizures, anti-epileptic treatments should preserve physiological network activity. Here, we used a thalamocortical slice preparation displaying physiological slow oscillations to investigate the effects of anticonvulsant drugs on physiological activity and epileptiform activity in two pharmacological epilepsy
The first highly potent and selective PDE8 inhibitors are disclosed. The initial tetrahydroisoquinoline hit was transformed into a nipecotic amide series in order to address a reactive metabolite issue. Reduction of lipophilicity to address metabolic liabilities uncovered an interesting diastereomer-dependent
Zolpidem is a widely prescribed sleep aid with relative selectivity for GABA(A) receptors containing alpha1-3 subunits. We examined the effects of zolpidem on the inhibitory currents mediated by GABA(A) receptors using whole-cell patch-clamp recordings from DMV neurons in transverse brainstem
A synaptosomal model was used to evaluate in vivo effects of paraoxon on the uptake of [(3)H]GABA in rat cerebral cortex and hippocampus. Male Wistar rats were given a single intraperitoneal injection of one of three doses of paraoxon (0.1
As a novel example of improved entry of poorly delivered drugs into the brain by means of nutrient conjugates, L-carnitine was conjugated to nipecotic acid and the capacity to antagonize PTZ-induced convulsions of this novel entity was evaluated.
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